Prescribing errors during hospital inpatient care: factors influencing identification by pharmacists

Objective: To investigate the prevalence of prescribing errors identified by pharmacists in hospital inpatients and the factors influencing error identification rates by pharmacists throughout hospital admission. Setting: 880-bed university teaching hospital in North-west England. Methods: Data about prescribing errors identified by pharmacists (median: 9 (range 4–17) collecting data per day) when conducting routine work were prospectively recorded on 38 randomly selected days over 18 months. Main outcome measures: Proportion of new medication orders in which an error was identified; predictors of error identification rate, adjusted for workload and seniority of pharmacist, day of week, type of ward or stage of patient admission. Results: 33,012 new medication orders were reviewed for 5,199 patients; 3,455 errors (in 10.5% of orders) were identified for 2,040 patients (39.2%; median 1, range 1–12). Most were problem orders (1,456, 42.1%) or potentially significant errors (1,748, 50.6%); 197 (5.7%) were potentially serious; 1.6% (n = 54) were potentially severe or fatal. Errors were 41% (CI: 28–56%) more likely to be identified at patient’s admission than at other times, independent of confounders. Workload was the strongest predictor of error identification rates, with 40% (33–46%) less errors identified on the busiest days than at other times. Errors identified fell by 1.9% (1.5–2.3%) for every additional chart checked, independent of confounders. Conclusions: Pharmacists routinely identify errors but increasing workload may reduce identification rates. Where resources are limited, they may be better spent on identifying and addressing errors immediately after admission to hospital.     

Factors predicting hospital readmissions related to adverse drug reactions

Objective  To analyse the contribution of adverse drug reactions (ADR) to hospital readmissions. Methods  This was a case–control study in which unscheduled admissions of patients who had been admitted to the hospital during the two previous months were assessed during a 21-month period. The patient was considered a case when the main diagnosis of readmission complied with the World Health Organisation’s definition of an ADR. For each case, two controls were selected from those patients that had been admitted for ADR without readmission (n = 177). Information on drugs and other risk factors was obtained from cases by interview and from controls by clinical record review. Results  There were 26,559 unscheduled admissions of which 81 were readmissions associated with ADR (4.5% of the unscheduled readmissions). There were no statistically significant correlations with sex, age or medical history, with the exception of arterial hypertension. The main drug products causing readmission were acenocoumarol (15, 18.5%), antihypertensive-diuretics (14, 17.3%), anticancer drugs (11, 13.6%) and digoxin (seven, 8.6%). In the multivariate logistic analysis, the variables predicting readmission were acenocoumarol [odds ratio (OR) 12.2, 95% confidence interval (CI) 3.8–38.3, P < 0.0001], a record of diabetes mellitus (OR 2.6, 95% CI 1.3–5.5, P < 0.01), the number of drugs taken at the moment of ADR (OR 1.2, 95% CI 1.1–1.4, P < 0.001) and high blood pressure (OR 0.3, 95% CI 0.2–0.6, P < 0.001) even though the latter was a negative predictor, preventing readmission. Of the 81 readmissions associated with ADR, 28 (34.6%) were preventable. Conclusion  A medical record of diabetes mellitus, polypharmacy and acenocoumarol treatment were risk factors predicting hospital readmission related to ADR.     

Relationship between drug-related problems and health outcomes: a cross-sectional study among cardiovascular patients

Objective To describe drug-related problems (DRPs) and expense problems (EPs) identified by a standardised community pharmacist-based medication review (MR) program among Swiss cardiovascular outpatients (56–75 years old) and to evaluate the need for collaborative pharmacy practice to achieve economic, clinical and humanistic outcomes. Setting A pilot population of 85 cardiovascular outpatients who were customers of 14 community pharmacies (members of the pharmacieplus virtual chain) and insured with Groupe Mutuel health insurance. Method Cross-sectional study of a structured medication review program, conducted by 11 pharmacists in collaboration with 61 general practitioners (GPs), with patient interviews and access to medical data. Main outcome measure Numbers and types of DRPs and EPs within the study population and odds ratios between them, as well as economic, clinical and humanistic outcomes. Results Of the included patients, 91% had at least one DRP or EP. The odds ratios indicated that not being exposed to DRPs was associated with a higher chance of reaching the clinical target (OR: 3.4; IC95%:1.1–10.5; P = 0.01), of having a better physical quality of life than the median (OR: 2.5; IC95%:0.9–7.3; P = 0.05) and having lower total health care costs (OR: 3.2; IC95%:1.1–9.8; P = 0.02). Conclusions This cross-sectional study shows that the control of cardiovascular risk factors, quality of life and healthcare costs are statistically related to the presence of DRPs detected by a community pharmacist-based MR program.     

Justification of the starting dose as the main determinant of accrual time in dose-seeking oncology phase 1 trials

Introduction New drug development is a time- and resource-consuming process. Phase 1 trials constitute a major key-step of this development. Shortening the accrual time is of major importance. Methods 292 published phase-1-trials were retrospectively reviewed to establish the determinants of accrual time using Log-rank test and then Cox Model. Results Out of 292 trials (1997–2008), only 107 reports (36%) described the accrual time (median: 20 months, 5–72). Phase-2-recommended dose was established in 87 studies (81%). Most studies investigated regimens including cytotoxic drugs (77%) or molecular targeted therapies (29%). Under univariate analysis, two parameters shortened the accrual time: studies conducted in USA vs. other places (19 vs. 21 months p = 0.03) and regimen with more than 2 dose-escalated drugs (13 vs. 21 months, p = 0.003). One parameter was significantly associated with longer accrual time: starting dose justified by animal toxicology data vs. previous clinical trials (22 vs. 19 months, p = 0.03). Most of parameters did not significantly affect the accrual time: nature of investigated drugs, duration of treatment cycle, phase 1 dedicated to specific tumoral subtypes, number of centers, method of drug escalation (classical 3+3 vs. accelerated titration design), type of increment (modified Fibonacci method vs. others) and presence of expansion of cohort at the phase-II-recommended dose. Cox model analysis retained one determinant: starting dose justified by animal toxicology data: HR = 2.00 [1.45–5.20], p = 0.047. Conclusion Few parameters influence the accrual time of dose-escalation phase-1 trials. Real first-in-man phase 1 studies based on starting dose estimated from animal toxicological data require longer accrual time.     

The preparation and administration of intravenous drugs before and after protocol implementation

Objectives This paper reports on a pilot study examining the incidence of nurses’ errors in preparation and administration of intravenous drugs. Furthermore, the study aimed to evaluate the short-term effects of implementation of a new protocol for preparation and administration of intravenous drugs. Setting Two nursing departments of internal medicine at a 953 beds University Medical Centre in The Netherlands. Methods By means of a prospective, quasi-experimental design, nurses were observed during the process of preparation and administration of intravenous drugs. Observation was performed before and after the implementation of a new protocol. Seventy-two nurses at two nursing departments were observed during the study. Main outcome measure A mean pre-test and post-test quality score at two departments of internal medicine. Results At baseline, average quality scores for nurses at the two departments were 64 (intervention ward) and 67 (control ward) on a 0–100 quality scale. The pre-test quality scores were not statistically significant for the two nursing wards (T = 1.36, df = 55, P = 0.18). After the implementation of the new protocol, nurses at the intervention ward scored better (72) than nurses at the control ward (69). The mean score at the intervention ward was significantly higher than the score in nurses of the control ward (T = −2.20, df = 53, P = 0.04). Conclusions The number of errors in the preparation and administration of intravenous drugs is high. This study shows that implementing a protocol for the preparation and administration of these drugs can reduce the number of errors.     

Medication persistence among patients with asthma/COPD drugs

Objective To determine medication possession ratio (MPR) of patients with asthma/COPD drugs. Method Individual patient’s volumes of asthma/COPD drugs (ATC-code R03) for 2000–2004 were obtained from a pharmacy record database. For each patient the MPR was calculated as the percentage of the treatment time that the patient had drugs available. Main outcome measure Medication possession ratio (MPR). Results A total of 1,812 patients, 20 years and older, with dispensed asthma/COPD drugs were registered in the database, 928 patients (51%) had acquired drugs less than once per year (68% for 20–29 years old) during the 5-year study. Only 13% of the patients had steroids and steroid combinations available to allow continuous treatment. Eight percent of the patients 20–29 years old had MPR ≥ 80% of all the included drugs and 5% when only steroids and steroid combinations were considered. About 25% of the patients had acquired 80% of the total volume of asthma/COPD drugs. Conclusion The majority of the patients, and particularly those in the youngest age group used asthma/COPD drugs only sporadically. This may indicate undermedication which is likely to have a negative impact on patient outcome.     

Safety of an injection with a mixture of extracts from Herba Artemisiae annuae, Fructus Gardeniae and Flos Lonicerae

Objective This study aimed to evaluate the safety for an injection with a mixture of extracts from Herba Artemisiae annuae, Fructus Gardeniae and Flos Lonicerae and to determine the risk factors that may affect its adverse drug reactions. Methods A drug-oriented prospective observational study was performed. Physicians filled in clinical observation forms with detailed information of the patients including general information, drug information, therapeutic effects and adverse drug events. The adverse drug reaction factors were analyzed by both mono-factor and multiple-factor logistic regression methods. Results From April to July 2007, we collected 12,427 observation forms from 46 hospitals in Jiangsu Province of China. Among the 11,707 observation forms we analyzed, 8,074 patients were children younger than 14 years old (69%). Among 51 reported adverse drug events, 45 cases were adverse drug reactions. The total adverse drug reaction incidence of the injection was 0.38%. While most adverse drug reactions were previously known (e.g., rash, pruritus, vomiting and diarrhea), we observed three new ADR symptoms: shiver, phlebitis and anhelation. All the adverse drug reactions were controlled very well through the follow-up therapy, and none of them was life threatening. The mono-factor analysis showed that adverse drug reactions of the injection were significantly correlated with total medication dose (P = 0.0049) and combination medication (P = 0.0143), especially with antimicrobial drugs (P = 0.0079) and macrolides (P = 0.0017). The multiple factor analysis confirmed these results: medication dosage and combination medication had a crucial impact on adverse drug reactions of the injection; the risk was increased by 24.8% (the estimated value of relative risk was 1.248, 95% confidence interval: 1.054–1.479) and 89% (1.890, 1.001–3.566), respectively. Conclusion The total adverse drug reaction incidence of the injection was 0.38% and lower than we expected. Moreover, we observed three new adverse drug reactions, none of which was severe.

Raising the awareness of inpatient nursing staff about medication errors

Objective The study objective was to design and implement an educational programme to raise the awareness of in-patient nursing staff about medication errors and other medication-related safety issues. Method A sample of in-patient nursing staff in Al Ain hospital (n = 370) was included in the study and completed a self-reported questionnaire about medication errors. A structured program was developed and used by the clinical pharmacists to identify the nursing knowledge on medication errors and other medication-related safety issues. The program consisted of a pre/post self-reported questionnaire, a training service, educational material, successive presentations and handouts. The self-reported questionnaire included twenty closed questions asking nurses opinions about medication errors. A training program on medication safety (Med Safe? tool) was carried out by [clinical pharmacy team (n = 2) and quality coordinator nurse (n = 1)], for each group of 10 nurses. Main outcome measure The study outcomes were the change in mean scores pre and post intervention. Results Findings revealed differences in the knowledge of nurses about the causes and reporting of medication errors. There were statistically significant differences in responses across the participant's years of experience and the current clinical working area. The participant's responses improved significantly [57.4% ± 8.2, (95%CI: 56.6–58.2) vs. 68.9 ± 10.3, (95%CI: 67.8–69.9); P < 0.05] pre and post questionnaire respectively. Conclusions The clinical pharmacist's structured program has improved knowledge of the in-patient nursing staff in terms of raising their awareness about medication errors.     

A pilot study of S-1 plus cisplatin versus 5-fluorouracil plus cisplatin for postoperative chemotherapy in histological stage IIIB-IV (M0) gastric cancer

Background Although its efficacy is unproven, 5-fluorouracil plus cisplatin (FP) is used to prevent postoperative relapse in gastric cancer. We investigated the safety and feasibility of S-1 plus cisplatin (SP) vs. FP for stage IIIB-IV (M0) gastric cancer. Methods Following curative resection, 41 stage IIIB-IV (M0) gastric cancer patients were assigned to SP (eight 14-day cycles of S-1 [40 mg/m² twice daily] plus cisplatin [60 mg/m² day 1] administered every 3 weeks) or FP (six 3-day cycles of FU [1 g/m² per day] plus cisplatin [80 mg/m² day 1] every 4 weeks). Doses were reduced based on predefined criteria. Results Patient characteristics were balanced between the two arms. In total, 124 cycles of SP (N = 20, median = 7, range 1–8) and 113 cycles of FP (N = 21, median 6, range 1–6) were administered. The median relative dose intensity per patient was 75% (49.99–100%) for S-1, 100% (75–100%) for cisplatin in SP, and 100% (64–100%) for 5-FU, 100% (60–100%) for cisplatin in FP. The relative dose intensity of FP was stable, while that of SP decreased during treatment. After median follow-up of 7.9 months (3.8–14.55), the median RFS was not reached. Relapse occurred in two (10%) patients on SP and five (23.8%) in the FP arm (P = 0.24). The incidence of grade 3–4 granulocytopenia was 36.8% with SP and 14.3% with FP. Grade 3–4 non-hematologic toxicities included fatigue (5.2% with SP vs. 4.8% with FP), vomiting (10.5% with SP vs. 0% with FP), and infection (5.2% with SP vs. 0% FP). Conclusion S-1 plus cisplatin was feasible and tolerable as adjuvant treatment for stage IIIB-IV (M0) gastric cancer. However, because of decreased relative dose intensity during treatment, further study is warranted to determine optimal dosage and combination.     

Genetic determinants of methotrexate toxicity in rheumatoid arthritis patients: a study of polymorphisms affecting methotrexate transport and folate metabolism

Objective  Methotrexate (MTX) is a disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis (RA). Genetic polymorphisms of reduced folate carrier (RFC1 A80G), P-glycoprotein (MDR1 G2677T>A/C and C3435T), 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TS 2R→3R), methionine synthase (MS A2756G) and methionine synthase reductase (MTRR A66G) modify MTX transport and metabolic effects and may influence the treatment response. Methods  A genotyping approach was used to determine the studied polymorphisms in 213 RA patients. Results  We observed that 56 (26.3%) patients discontinued MTX treatment due to poor response and/or toxicity. RFC1 A80G and MDR1 C3435T polymorphisms increased the risk for overall MTX toxicity (P = 0.039, OR = 3.574, 95% CI = 1.065–11.993 and P = 0.032, OR = 7.801, 95% CI = 1.194–50.960 respectively), while MTHFR A1298C polymorphism had a protective effect on overall MTX toxicity (P = 0.027, OR = 0.170, 95% CI = 0.035–0.820). Conclusion  Our results suggest that genetic polymorphisms in the folate metabolic pathway and MTX transporters modify the toxicity but not the efficacy of MTX treatment.     

Women encounter ADRs more often than do men

Background  Several publications indicate that the female gender experiences a higher incidence of adverse drug reactions (ADRs) than does the male gender. The reasons, however, remain unclear. Gender-specific differences in the pharmacokinetic and pharmacodynamic behaviour of drugs could not be identified as an explanation. The aim of this study was to analyse ADR risk with respect to gender, age and number of prescribed drugs. Methods  A prospective multicenter study based on intensive pharmacovigilance was conducted. Information on patient characteristics and evaluated ADRs was stored in a pharmacovigilance database—KLASSE. Results  In 2,371 patients (1,012 female subjects), 25,532 drugs were prescribed. In 782 patients, at least one ADR was found. A multivariate regression analysis adjusting for age, body mass index (BMI) and number of prescribed drugs showed a significant influence of female gender on the risk of encountering ADRs [odds ratio (OR) 1.596, confidence interval (CI) 1.31–1.94; p < 0.0001). Dose-related ADRs (51.8%) were the dominant type in female subjects. Comparing system organ classes of the World Health Organisation (SOC-WHO), cardiovascular (CV) ADRs were particularly frequent in female subjects (OR 1.92, CI 1.15–3.19; p = 0.012). Conclusion  Our data confirm the higher risk of ADRs among female subjects compared with a male cohort. Several explanations were investigated. No single risk factor could be identified.     

Antipsychotic-induced Extrapyramidal Syndromes in Psychiatric Practice: A Case-control Study

Background: While several clinical trials showed that atypical antipsychotics have a low risk of extrapyramidal side effects (EPS), this observation is not undisputed. This study compared the risk of EPS between specific subgroups of antipsychotics. Methods: Using the automated dispensing records of a large psychiatric hospital in The Netherlands, we defined cases as first-time users of anticholinergic antiparkinson drugs. Controls were all patients with no recorded use of such medication. Cases and controls were compared with regard to previous use of antipsychotics and relevant co-factors. Results: Out of 1403 patients, we identified 105 cases and 330 controls. Compared to non-users, antipsychotic-users were 10 times more likely to start with anticholinergic antiparkinson medication (adjusted odds ratio: 10.1; 95 CI 4.6–22.3). Depot and non-depot antipsychotics had similar adjusted odds ratios of 10.9 (95 CI 3.7–32.6) and 8.8 (95% CI 3.8–20.4) respectively. Low and high potency antipsychotics gave odds ratios of 3.0 (95% CI 0.9–10.3) versus 10.8 (95% CI 4.7–25.1). Classical and atypical antipsychotics showed comparable odds ratios: 10.0 (95% CI: 4.4–22.5) versus 8.0 (95% CI: 2.6–24.5). Applied doses of classical and atypical antipsychotic drugs were much lower and more equivalent than those used in previous clincial trials. Conclusions: Low potency antipsychotics had a much lower risk of EPS than other antipsychotics. However, we did not corroborate the reduced risk with atypical antipsychotics observed in several clinical trials. This discrepancy may result from the high and non-equivalent doses of classical antipsychotics used in many of these trials.     

Adverse events of blood-pressure-lowering drugs: evidence of high incidence in a clinical setting

Objectives  Our primary objective was to determine the incidence of AEs of antihypertensive drugs in a cohort of outpatients attending a specialized clinic. The secondary objectives were to determine the incidence of AEs by classes of blood-pressure-lowering drugs used in monotherapy and to identify risk factors for the occurrence of AEs. Methods  In a prospectively planned cohort study, patients attending a hypertension outpatient clinic were systematically interrogated about the occurrence of AEs of blood-pressure-lowering drugs. We compared the incidence of AEs by classes of drugs employed in monotherapy and identified risk factors for the occurrence of AEs in a logistic regression model. Results  Participants were followed for 12.3 ± 12.2 months. In total, 534 (35.4%) of 1,366 patients treated with blood pressure drugs complained of at least one AE during the follow-up, corresponding to an incidence of 31.3 AEs per 1,000 patients/month [95% confidence interval (CI) 28.6–33.9). The systolic blood pressure in the initial evaluation (P = 0.002) and use of two or more drugs (P < 0.001) were associated with higher incidence of AEs. The incidence of AEs was higher among patients treated with calcium channel blockers in monotherapy than in patients treated with diuretics (47.2 vs. 7.6%, P < 0.001). Conclusion  Adverse events of blood-pressure-lowering drugs are quite frequent in a clinical context, and may influence the adherence to treatment. Patients under treatment with diuretics in monotherapy have the lower incidence of AEs.     

The federal standard medication plan in practice: An observational cross-sectional study on prevalence and quality

BackgroundMedication plans are instruments used to document drug therapies, guide patients, and ensure medication safety. In Germany, patients who take at least 3 long-term medications are eligible to receive a medication plan. It has been statutory to use the federal standard layout (German: “Bundeseinheitlicher Medikationsplan”) since April 2017.ObjectivesThis study explores the prevalence, availability, medication discrepancies, and conformance with statutory regulations of medication plans since the introduction of the format of the federal standard medication plan in Germany.MethodsMedication reconciliation was performed for hospitalized patients according to the Best Possible Medication History principle. The collected medication lists were analyzed for medication discrepancies and conformance with the statutory regulations. The medication discrepancies were (1) omitted drugs, (2) additional drugs, and (3) dosing errors.ResultsAfter hospitalization, 524 patients taking drugs were included. The majority (n = 424 patients) were eligible for a medication plan. While 241 medication lists were present, only 24.1% (n = 58) matched the federal standard format. The mean number of drugs was 6.3 ± 3.6, with 3315 medications (3046 long-term and 269 as needed) reconciled totally. The 84 medication lists with omitted or additional drugs included 166 medication discrepancies upon 774 drugs listed. Of the 253 patients with dosing errors, 146 had a medication list. Inappropriate dosages were due to single dose (n = 195), daily dose (n = 225) or frequency of application (n = 255).ConclusionMedication plans are valuable tools for patients and health care providers. This study shows that the introduced paper-based federal standard medication plan in Germany falls short of its expectations regarding availability and correctness. Switching to an electronic patient record system may overcome some of the current pitfalls.     

CYP2D6*4, CYP3A5*3 and ABCB1 3435T polymorphisms and drug-related falls in elderly people

Objective The objective of this study is to investigate the association between CYP2D6*4, CYP3A5*3 and ABCB1 3435T polymorphisms and drug-related falls. Method Multivariate logistic regression was performed in an existing database in order to study the association between falls history and CYP2D6*4, CYP3A5*3, ABCB1 3435T polymorphisms in patients using fall-risk-increasing CYP2D6, CYP3A5 and P-glycoprotein (gene product of ABCB1) substrates. Results No statistically significant increased fall risk was found in ‘poor metabolizers’ compared to ‘extensive’ and ‘intermediate metabolizers’ using fall-risk-increasing CYP2D6 substrates (Odds ratio (OR) = 2.2; 95% confidence interval (CI) 0.2–25.0), CYP3A5 substrates (OR = 0.9; 95% CI 0.2–3.3) and P-glycoprotein substrates (OR = 2.1; 95% CI 0.2–17.2). Conclusion The hypothesis that ‘poor metabolizers’ have an increased fall risk was not confirmed. A larger study population is needed to confirm the potential association that was seen between CYP2D6*4 and ABCB1 3435T polymorphisms and drug-related falls.     

The effect on medication errors of pharmacists charting medication in an emergency department

Objective To determine the frequency and clinical significance of medication errors when (a) pharmacists elicit medication histories in the Emergency Department after medications have been prescribed by doctors and (b) pharmacists obtain and chart medication histories prior to doctors’ approval. Setting The Queen Elizabeth Hospital, a 350 bed South Australian teaching hospital, serving the local adult community. Method Emergency Department patients at risk of medication misadventure were recruited in two phases with a ‘usual practice’ arm (6 weeks) and a ‘pharmacist medication charting’ arm (5 weeks) reflecting an alternative intervention. In the ‘usual care’ arm, medication histories were compiled by a pharmacy researcher after a doctor had completed the medication chart. The researcher-elicited medication histories were compared with the doctors’ medication charts and unintentional discrepancies were recorded. In the ‘pharmacist medication charting’ arm, the same process was followed except the researcher compiled the patients’ medication histories at triage, prior to patients seeing a doctor. The medication history was then transcribed onto a medication chart for authorisation by a doctor. In addition, whether resolution of unintentional discrepancies for patients in the ‘usual care’ arm had occurred by discharge was determined by examining patients’ medical records. Main outcome measure Frequency of unintentional discrepancies and medication errors. Results The study included 45 and 29 patients in the ‘usual care’ and intervention arms, respectively. In the ‘usual care’ arm, 75.6% of patients had one or more unintentional discrepancies compared with 3.3% in the ‘pharmacist medication charting’ arm. This resulted in an average of 2.35 missed doses per patient in the ‘usual care’ arm and 0.24 in the intervention arm. In addition, an average of 1.04 incorrect doses per patient were administered in the ‘usual care’ arm and none in the ‘pharmacist medication charting’ arm. The differences observed between the arms were statistically significant (P < 0.05) and deemed clinically significant by a multidisciplinary panel. Conclusion This study provides evidence for pharmacists eliciting medication histories to prepare medication charts at the earliest possible opportunity following a patient’s presentation to the Emergency Department